The proposed research constitutes a genetic analysis of factors responsible for cell-type-specific gene expression in differentiated cells. The expression of a variety of liver-specific traits in cultured hepatoma cells and in novel somatic cell hybrids will be studied in order to define and characterize loci involved in specialized gene expression. The basic methodology to be employed is microcell mediated chromosome transfer, a technique in which single or limited numbers of intact chromosomes are transferred from one mammalian cell to another. This approach will be used to determine whether specific genetic loci suppress the expression of particular liver-specific traits in cells of non-hepatic origin. Conversely, the action of genes which function to activate hepatic phenotypes in liver-derived cells will be studied. The linkage relationships among loci which exert regulatory effects on specialized gene expression and the structural genes of liver-specific products will be determined. In this way it will be possible to gain insight into the coordination and/or hierarchy of control involved in the maintenance of a particular developmental program. Particlar genes which regulate expression of specific traits will be further analyzed in order to study changes which occur in these loci as a cell follows a given path of differentiation.